1. Principles of antibiotic therapy in paediatrics
Dr. György Fekete

2. Special pediatric considerations
Immunology
Pharmacokinetics
Overuse of antibiotics
Mistake: fever = antibiotic therapy
Except: neutropenia!

3. Antimicrobial Programme
Reduction of healthcare associated infections
Slowing the development of antimicrobial resistance
Right Drug, Right Dose, Right Time, Right Duration

4. 1. What is the reason? Indication?
Antibiotics
1. What is the reason? Indication?
- local infection (skin, pneumonia, UTI, etc.)
- empiric and targeted teatment
- fever + general symptoms (CRP, WBC count and smear, procalcitonin, etc.)

5. Do not start antibiotics without evidence of bacterial infection!
History of allergies – atopic allergy
Penicillin hypersensitivity: 1 – 10%, anaphylactic reactions < 0.05%
0.5 – 6.5% of patients allergic to penicillins: also allergic to cephalosporins
Start prompt effective treatment within one hour of diagnosis: severe sepsis, lifethreatening infections

6. To prescribe
antibiotics which are likely to be bactericidal to the pathogen at the site of infection
in adequate dosis + adequate duration
for the shortest duration likely to be effective

7. Precise documentation
Clinical indication
Dose and route of administration
Drug chart + clinical notes
Review/ stop date or duration
All sensitivity results
Consultation with microbiologist

8. 2. Previous microbiological investigations?
- Gram staining
- throat
- urine
- haemoculture
- cerebrospinal fluid
- pleural, synovial fluid
- rapid tests (Str.pyogenes,
S. pneumoniae, H. influenzae antigens)

9. 3. What is the potential (bacterial) cause of infection
3. What is the potential (bacterial) cause of infection? - age (newborn, infant, toddler…) - medical procedure, hospitalisation - immune deficiency - organ damage (spleen, liver, kidney)

10. Localizing symptoms Skin Upper respiratory Lower respiratory
Genitourinary
Gastrointestinal
CNS
Skeletal
Cardiovascular
Hepatic

11. Skin: Sta. aureus, Str. pyogenes Tonsillopharyngitis 15-20%:
Deep infections: anaerobic, Gram negative
Tonsillopharyngitis 15-20%:
Str. pyogenes
Differential dg:infectious mononucleosis
Cystic fibrosis: pulmonary infection, Pseudomonas aeruginosa
Diabetes mellitus: Sta.aureus

12. Neonatal sepsis /meningitis
Focal infection: pneumonia, RDS
Group B streptococci, E. coli, other Gram-negative rods, Listeria monocytogenes, S. aureus
Th: Ampicillin+ cefotaxim
Third generation cephalosporin instead of aminoglycoside

13. Bacterial meningitis in children, 2 months to 12 yrs
Str. pneumoniae, N. meningitidis (B,C)
(H. influenzae type b)
Therapy: 1 – 3 months: - cefotaxime / ceftriaxone + ampicillin +vancomycin
>3 months:cefotaxime/ceftriaxone +vancomycin

14. Bacterial meningitis
Empiric therapy: < 3 months: IV Cefotaxime + IV Amoxicillin
> 3 months: IV Ceftriaxone
Neisseria meningitidis: Iv cefotaxime 7 days (+ IV Vancomycin)
Group B Streptococcus: IV Cefotaxime 14 days
Gram negative infections: IV cefotaxime 21 days

15. Listeria monocytogenes: IV amoxicillin 21 days + Gentamicin in the first 7 days

16. 4. Which antibiotic will be optimal? First choice?
- data of bacterial resistance
(enterococci are resistant to cephalosporins)
- site of infection – penetration?
- side effects?
- bactericide effect
- administration: 1x / day
- not expensive

17. Resistant clones of microorganisms
Str. pneumoniae
Staph. aureus
Virulent
Serious infections
Overuse of antibiotics
Viral infections
Broad spectrum antimicrobial agents

18. 5. Any combination is appropriate?
- nosocomial infection
- sepsis (focal infection is not known,granulocytopenia)
- abdominal and pelvic infections
- endocarditis
- empiric treatment
- active tuberculosis

19. Susceptibility testing
It is the opportunity to avoid broader spectrum (and more expensive) antibiotics when a more narrowly active (and cheaper) drug is effective!

20. No combination therapy is necessary in cases of „non-hospital” infections
Exception: the doctor can not decide whether pneumonia is „typical” or „atypical”
Therapy: beta- lactam+ macrolid antiobiotics
Atypical pneumonia syndrome: Legionella, Chlamydia trachomatis (psittaci, pneumoniae), Mycoplasma pneumoniae

21. Active tuberculosis Treatment: INH, rifampin, pyrazinamide
Ethambutol, ethionamide

22. 6. Metabolism, excretion? - kidney, liver (monitoring)
- renal: aminoglycosides
- liver: erythromycin, clindamycin, ceftriaxon
- maternal antiobiotic treatment during breast – feeding (chloramphenicol, tetracyclin,sulfonamids,metronidasol)
7. Mode of administration
- iv, oral
- „switch”

23. Iv. administration (initial 2 weeks)
Sepsis, meningitis
Endocarditis
Liver abscess
Osteomyelitis
Septic arthritis
Empyema
Cavitating pneumonia

24. Long-term hypotension
Hemorrhagic diathesis
Severe or necrotising soft tissue infections
Intracranial abscesses
Intra – abdominal sepsis
Exacerbation of cystic fibrosis
Severe infections during chemotherapy- related neutropenia

25. Switching from IV to oral administration
Clinical improvement
The patient is medically stable

27. 8. Dosage. Body surface, body weight Special doses in neonates 9
8. Dosage ? Body surface, body weight Special doses in neonates 9. Changing of antiobiotic drug? Indications? 10. How long should we treat? - Preterm and newborn babies need antibiotic therapy of longer duration (sepsis, bacterial meningitis, etc.)

28. Optimal duration of antibiotic therapy
Streptococcal tonsillopharyngitis: penicillin/ 10days
Acute osteomyelitis: 4-6 weeks
UTI: days (multiresistant Gram negative bacteria: 4-6 weeks)

29. Antimicrobial prophylaxis
Neonatal conjunctivitis
Chlamydia trachomatis
0.5% erythromycin topically
Neisseria gonorrhoeae
1% silver nitrate or

30. Antimicrobial prophylaxis
Splenectomy / asplenia
Str. pneumoniae
Penicillin

31. Antimicrobial prophylaxis
Prevention of early-onset B group Streptococcus infection
Maternal screening ( gestational week)
Iv. ampicillin, or clindamycin, erythromycin

32. Antimicrobial prophylaxis
Rheumatic fever
Long-term Penicillin prophylaxis
Recurrent UTI ( vesio-ureteral reflux, etc.)
Bacterial endocarditis

33. Broad - spectrum antimicrobial agents
Drastic changes in bowel flora
Bleeding disorders
Emergence of resistant organisms
Superinfections: yeasts, enterococci

34. Cellulitis (phlegmone)
Inflammation of the
subcutaneous connective
tissue – may lead to abscess
Streptococcus pyogenes,
Staphylococcus aureus,
Haemophilus influenzae (<2 yrs)
Therapy: IV penicillin+ clindamycin, flucloxacillin

35. Erysipelas Group A Streptococcus, Staph. aureus
Therapy: phenoxymethylpenicillin
Staph. aureus: PO flucloxacillin (beta –lactam antibiotic of the pnicillin class)

37. Tonsillitis, tonsillopharyngitis
Streptococcus pyogenes : Penicillin for 10 days
Penicillin allergy: macrolid antibiotics
Non- Streptococcus origin: amoxicillin, amoxicillin+ clavulanic acid, macrolids, cephalosporin antibiotics

38. Epiglottitis Emergency! 2-7 yrs
Haemophilus influenzae type B (vaccination)
Sudden onset of fever
Dysphagia, muffled voice, cyanosis, stridor, inspir. retractions
Progression to total airway obstruction
Th: endotracheal intubation, ceftriaxone iv.
Manipulate as little as possible!

40. Pediatric pulmonary diseases
50% of deaths under age of 1 yr
20% of all hospitalisations under age of 15 yrs
7% of children: chronic disorder of the lower respiratory system

41. Most common diseases Viral upper respiratory infections Otitis media
Pneumonia
Asthma
Cystic fibrosis

42. Symptoms Dyspnea, tachypnea, hyperpnea Cough Chest pain
Rales(crackles), rhonchi
Wheezing
Retractions
Fever

43. Bacterial pneumonia
Risks: aspiration, immunodeficiency, tracheoesophageal fistula, cleft palate, CF, congestive heart failure, splenectomia,etc.
Fever, cough, dyspnea, meningismus, abdominal pain, otitis media
Laboratory findings: elevated WBC, CRP
Chest X-ray
Age-specific bacteria
Complications: empyema, sepsis, abscesses

44. Diagnostic measures History (parents, child)
Inspection (flaring of alae nasi)
Auscultation (take a deep breath: blow out a candle)
Respiratory rate (younger than 1 year: 25-35/min, sleeping)
Imaging techniques
Arterial blood gas analysis
Pulse oximetry, capnography
Pulmonary function testing
Laryngoscopy, bronchoscopy

47. Uncomplicated community acquired pneumonia
<5 years : PO amoxicillin (+macrolide if no response)
5 – 18 yrs: PO amoxicillin + PO clarithromycin

48. Hospital acquired pneumonia
IV ceftazidime (+IV gentamicin in Pseudomonas aerug. infection)
IV Vancomycin + IV Aztreonam

49. Urinary tract infections
Children <3 months with possible
UTI infection: IV Cefotaxime+
IV Amoxicillin
Acute pyelonephritis > 3 months:
IV Ceftriaxone, 72 hrs, then review. Step down to PO cefalexin

50. Specific therapeutic values
Vancomycin: methicillin-resistant staphylococci
Metronidazole: anaerobic infections
Ceftazidine: Pseudomonas aeruginosa
Trimethoprime+ sulfamethoxazole: shigellosis, salmonellosis, Pneumocysis carinii ( pentamidine)

51. Local (hospital) microbiological laboratory
Knowing the prevalence of antibiotic – resistant organisms in a particular community (nursery) is helpful in choosing the first-line antibiotic regimens

56. Test of efficacy= patient’s response
No respond to seemingly appropriate therapy: reassessment is needed!
In some infections additional supportive treatment ( surgical) is necessary

57. Anaerobic infections Oropharynx, gastrointestinal tract, vagina, skin
Gram- negative nonsporulating rods: Bacteroides, Fusobacterium
Gram-positive nosporulating rods: Eubacterium, Propionibacterium

58. Anaerobic infections
Neonates: prolonged rupture of membranes, amnionitis, obstetric difficulties
Peritonitis, appendicitis
Aspiration pneumonia with lung abscess
Orofacial infections
Brain abscess

59. Anaerobic infections/ treatment
Cefoxitin, amoxicillin/ clavulanate, clindamycin
Metronidazole
Cefotetan
Imipenem, merapenem
Piperacillin, tazobactam

60. CEPHALOSPORIN ANTIBIOTICS 1
CEPHALOSPORIN ANTIBIOTICS 1. generation drugs Cefazolin (Kefzol) does not cross the blood- brain barrier. No use for initial th. of sepsis / meningitis Cefalexin (Keflex. Ospexin) Cefadoxil (Duracef)

61. 2. generation drugs Cefamandol (Mandokef) Cefuroxim (Zinnat, Zinacef) Cefoxitin (Mefoxin) Cefaclor (Ceclor)

62. 3. generation drugs Cefotaxim e (Claforan) Ceftriaxone (Rocephin) Cefoperazon (Cefobid) Ceftazidim ((Fortum) Cefixim (Suprax) Ceftibuten (Cedax)

63. 4. generation drug Cefepim (Maxipime) Cefpirom

64. PENICILLIN Penicillin G V Streptococcus procain-penicillin Str
PENICILLIN Penicillin G V Streptococcus procain-penicillin Str. pneumoniae

65. METHICILLIN Oxacillin Staphylococcus aureus Nafcillin

66. AMINOPENICILLIN (ampicillin , amoxicillin) Streptococcus B Str
AMINOPENICILLIN (ampicillin , amoxicillin) Streptococcus B Str. pneumoniae Listeria

67. AMINOPENICILLIN beta+-lactamase respiratory , inhibitor urinary tract infections (ampicillin+sulfactam, amoxicillin+clavulanic acid)

68. UREIDOPENICILLIN mezlocillin, piperacillin (+beta-lactamase inhibitor as well) piperacillin/tazobactam Severe systemic infections

69. Tetracyclines Contraindicated before the age of 10 yrs! Good effect:
Chlamydia, Mycoplasma, Actinomyces, Lyme disease, pelvic infections, urethritis, brucellosis
Contraindicated before the age of 10 yrs!

70. ANTIBIOTIC DRUGS Active ingredient Product Amoxicillin Aktil, Augmentin + clavulanic acid Ampicillin Ospamox, Penstabil, Pentrexyl

71. Active ingredient Product Ampicillin Unasyn +Sulbactam Azithromycin Sumamed Azlocillin Securopen

72. Active ingredient Product Cefadroxil Duracef Ceftazidime Fortum Ceftriaxon Rocephin Cefixim Suprax

73. Active ingredient Product Cefepime Maxipime Ceftibuten Cedax Cefoperazon Cefobid Cefotaxim Claforan

74. Active ingredient Product Cefuroxim Zinacef, Zinnat Clarithromycin Klacid Clindamycin Dalacin C Ciprofloxacin Ciprobay, Cifran, Supplin

75. Active ingredient Product Imipenem Tienam + cilostatin Josamycin Wilprafen Meropenem Meronem Metronidazol Klion

76. Active ingredient Product Mezlocillin Baypen Netilmicin Netromycine Penicillin Maripen, Ospen, Vegacillin

77. Active ingredient Product Sulfamethoxazol Sumetrolim, +trimethoprim Bactrim, Cotrimel Teicoplanin Targocid Tobramycin Brulamycin Vancomycin Vancocyn